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Figure 3: Fifty simulations for the numbers and sizes of metastases. In these simulations the primary tumors were presumed successfully resected from each host. All biological properties of the tumors and hosts were assumed constant. The only sources for deviation were random chance and heterogeneities in regional organ blood flow. In each simulation there were no clinically detectable metastases at the time of surgery, and the individuals were restaged after a time to allow for 12 volume doublings. a. Simulated numbers of metastases. Using the same parameterization as employed in Fig. 1, six cases sustained no metastases whereas the remaining cases sustained anywhere from one to just under forty metastases. b. Simulated sizes of metastases. The resultant sizes of metastases from each case are plotted here semi-logarithmically. The right axis provides the numbers of cells per metastasis; the left gives the corresponding diameters of the metastases. Many of these metastases would likely be below the threshold of conventional clinical detection (arbitrarily defined here as at 109 cells). Given additional time for growth the subclinical metastases would have also become overt.

Image Text (High Precision): Tumor case cells metastases metastasis size

Other Images from "Chance mechanisms affecting the burden of metastases":


Figure 4 Detection of metastases. The percentage ...

Figure 1 Frequency distribution for the numbers o...

Figure 2 Size distribution for metastases. A mode...

Figure 3 Fifty simulations for the numbers and si...

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Abstract

BackgroundThe burden of cancer metastases within an individual is commonly used to clinically characterize a tumor's biological behavior. Assessments like these implicitly assume that spurious effects can be discounted. Here the influence of chance on the burden of metastasis is studied to determine whether or not this assumption is valid.MethodsMonte Carlo simulations were performed to estimate tumor burdens sustained by individuals with cancer, based upon empirically derived and validated models for the number and size distributions of metastases. Factors related to the intrinsic metastatic potential of tumors and their host microenvironments were kept constant, to more clearly demonstrate the contribution from chance.ResultsUnder otherwise identical conditions, both the simulated numbers and the sizes of metastases were highly variable. Comparable individuals could sustain anywhere from no metastases to scores of metastases, and the sizes of the metastases ranged from microscopic to macroscopic. Despite the marked variability in the number and sizes of the metastases, their respective growth times were rather more narrowly distributed. In such situations multiple occult metastases could develop into fully overt lesions within a comparatively short time period.ConclusionChance can have a major effect on the burden of metastases. Random variability can be so great as to make individual assessments of tumor biology unreliable, yet constrained enough to lead to the apparently simultaneous appearance of multiple overt metastases.


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